Electrophoresis analysis apparatus and sample vessel used therefor

ABSTRACT

A multi-capillary type electrophoresis analysis apparatus has a sample tray for containing a plurality of samples, wherein part of the sample tray is made from a conductive material. Samples are introduced by applying a high voltage from a high voltage power supply between the sample tray and a coupler in a state in which one-ends of the capillaries are inserted in the samples contained in the sample tray. The apparatus eliminates the necessity of individually inserting electrodes in a plurality of samples contained in the sample tray, thereby making easy works for analysis.

BACKGROUND OF THE INVENTION

[0001] The present invention relates to an electrophoresis analysisapparatus and a sample vessel used therefor, and particularly to anelectrophoresis analysis apparatus suitably used for a DNA sequencer(DNA base sequence analyzer) for analyzing biochemical samples such as aDNA (Deoxyribonucleic acid) using a plurality of capillaries ormicropassages as migration separation media, and a sample vessel usedtherefor.

[0002] A DNA analysis technology based on electrophoresis, particularly,a DNA sequencer (DNA base sequence analyzer) has been widely available.With the raised need for analysis, the necessity of improving theanalysis throughput has been increased. One method of increasing theanalysis throughput is to integrate electrophoresis media.

[0003] A thin gel layer formed between two flat glass plates has beenconventionally used as electrophoresis separation media. On the otherhand, a multi-capillary method using a plurality of capillaries eachhaving a fine inside diameter has been proposed, for example, in Nature,Vol. 361 (1993), Kanbara, PP. 565-566, the specifications of U.S. Pat.Nos. 5,277,780, 5,366,608, and 5,274,240, Japanese Patent Laid-open No.Hei 5-72177, and PCT international publication for patent applicationNo. Hei 7-503322. Such a method makes it possible to increase the degreeof integration by making use of the fine inside diameters of thecapillaries and to simultaneously analyze a large number of samples. Inthis method, further, since the cross section of migration passagesbecomes smaller than that of the conventional flat glass plates, acurrent caused by electrophoresis becomes smaller to thereby suppressgeneration of a Joule heat. As a result, by applying a higherelectrophoresis voltage, a sample can be migrated at a higher speed.Accordingly, a number of samples can be simultaneously separated andanalyzed at a high speed.

[0004] As a second method, a multi-capillary method of making use offine grooves formed in a surface portion of a glass plate as migrationpassages has been proposed, for example, in the specification of U.S.Pat. No. 5,192,412 and Japanese Patent Laid-open No. Hei 5-93711. Evenin this method, a number of samples can be simultaneously separated andanalyzed at a high speed.

[0005] In the above-described multi-capillary method, one-ends of anelectrode and a capillary are first inserted in a sample contained in asample vessel, followed by applying a voltage across the capillary toelectrically migrate the sample into the capillary; and then theone-ends of the electrode and the capillary are inserted in a buffersolution in a buffer bath, followed by applying a voltage across thecapillary to separate the sample by electrophoresis.

[0006] In the case where the number of samples to be simultaneouslyanalyzed is several pieces, since the number of electrodes/capillariesis the same as that of the samples, it does not take a labor so much toinsert the electrodes and capillaries in sample vessels and a bufferbath.

[0007] However, in the case where several tens of samples aresimultaneously analyzed to improve the analysis throughput, it isdifficult to insert electrodes and capillaries in sample vessels and abuffer bath. To be more specific, the amount of a sample generally usedfor a DNA sequencer is merely 5 μl because it is difficult to prepare alarge amount of a sample and also a reagent to be used is expensive. Inthe case where the sample in an amount of 5 μl is put in a sample vesselhaving an inner diameter of 2 mm, the liquid level becomes only about1.5 mm. It is very difficult to individually insert several tens ofelectrodes and capillaries in the above small-sized sample vessels.

SUMMARY OF THE INVENTION

[0008] An object of the present invention is to provide amulti-capillary type electrophoresis analysis apparatus capable ofmaking easy works for analysis and a sample vessel used therefor.

[0009] According to the present invention, there is provided anelectrophoresis analysis apparatus having a plurality of migrationpassages and a detector for optically detecting a plurality of samplecomponents separated by electrophoresis, including: a sample vessel forcontaining a plurality of samples to be introduced in the migrationpassages, at least part of a portion, of the sample vessel, to be incontact with these samples being made from a conductive material;wherein the samples are introduced in the migration passages by applyinga voltage to the migration passages via the conductive material formingpart of the sample vessels. With this configuration, since part of thesample vessel can be used as an electrode and thereby insertion ofelectrodes in samples can be eliminated, it is possible to make easyworks for analysis.

[0010] The sample vessel preferably includes a plate portion having aplurality of openings and a metal base portion fixed on a bottom portionof the plate portion.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In the drawings:

[0012]FIG. 1 is a perspective view showing the entire configuration ofan electrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0013]FIG. 2 is a plan view of sample vessels used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0014]FIG. 3 is a sectional view taken on line A-A of FIG. 2;

[0015]FIG. 4 is a plan view of second sample vessels used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0016]FIG. 5 is a sectional view of third sample vessels used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0017]FIG. 6 is a sectional view of a fourth sample vessel used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0018]FIG. 7 is a sectional view of a fifth sample vessel used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0019]FIG. 8 is a sectional view of a sixth sample vessel used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0020]FIG. 9 is a sectional view of a seventh sample vessel used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention;

[0021]FIG. 10 is a plan view of an electrode portion of eighth samplevessels used for the electrophoresis analysis apparatus according to oneembodiment of the present invention; and

[0022]FIG. 11 is a plan view of an electrode portion of ninth samplevessels used for the electrophoresis analysis apparatus according to oneembodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] Hereinafter, preferred embodiments in which the present inventionis applied to an electrophoresis analysis apparatus and sample vesselsused therefor will be described with reference to FIGS. 1 to 11.

[0024] Referring first to FIG. 1, there will be described the entireconfiguration of the electrophoresis analysis apparatus according to oneembodiment of the present invention.

[0025]FIG. 1 is a perspective view showing the entire configuration ofthe electrophoresis analysis apparatus according to the embodiment ofthe present invention.

[0026] First, the entire configuration will be described below.

[0027] A migration buffer bath 12 containing a buffer (electrolyte) isdisposed on a moving mechanism 10. A platinum electrode 13 isstretchingly mounted in the migration buffer bath 12 in such a manner asto be in contact with the buffer. On the moving mechanism 10 are alsodisposed three sample trays 100A, 100B and 100C via a sample tray holder14. As will be described later with reference to FIG. 2, the sample tray100A includes 48 pieces of sample vessels. The sample tray 100A isremovably fixed on the sample tray holder 14 with set screws S1 and S2.The bottom portion of the sample tray 100A is made from a conductivemetal such as a stainless steel, and is electrically conductive to thesample tray holder 14 which is made from a conductive metal such as astainless steel. Similarly, each of the sample trays 100B and 100Cincludes 48 pieces of sample vessels and has a bottom portion which iselectrically conductive to the sample tray holder 14.

[0028] The moving mechanism 10 is vertically movable in the Z-axisdirection along vertical slide guides 18Z using a vertically movingmotor 16Z. The moving mechanism 10 is also longitudinally movable in theX-axis direction along longitudinal slide guides 18×using alongitudinally moving motor 16X. The motors 16Z and 16X are controlledby a controller 80. A transparent cover 19 made from polyvinyl chlorideor polyacrylate or polymethacrylate resin is disposed in such a manneras to cover the three sample trays 100A, 100B and 100C for suppressingevaporation of samples held in the sample vessels and preventingcontamination of the sample vessels with external dust.

[0029] The electrophoresis analysis apparatus includes 48 pieces ofcapillaries 20 disposed in parallel, each of which is filled with a gelmatrix for separation. The lower end sides of the capillaries 20 arefixed by capillary retaining plate 22, and the lower ends of thecapillaries 20 are inserted in the buffer in the migration buffer bath12. The upper end sides of the capillaries 20 are fixed by a capillaryretaining plate 24, and the upper ends of the capillaries 20 are fixedlyconnected to a coupler 26.

[0030] The coupler 26 is connected to an electrode plug 32 on the earthside, and the electrode plug 32 is in turn connected to an earthelectrode of a high voltage power supply 30. The sample tray holder 14is connected to an electrode plug 34 on the high voltage side, and theplatinum electrode 13 in the buffer bath 12 is connected to an electrodeplug 36 on the high voltage side. The electrode plugs 34 and 36 areconnected to a high voltage (−) electrode of the high voltage powersupply 30.

[0031] The coupler 26 is connected to a sheath flow cell 40, into whicha sheath liquid 44 held in a sheath liquid tank 42 is introduced by thegravity. Samples, which are separated by migration in the capillaries 20and flow out of migration terminals of the capillaries 20, are carriedto the upper side with the sample components in the capillaries left asseparated.

[0032] Laser light emitted from a laser 50 is collimated into parallellight beams by a lens 52, and the sheath flow cell 40 is irradiated withthe laser beams from its side surface (in the Y-direction in thedrawing), to excite the separated sample in the sheath flow cell 40. Ashutter 54 is provided between the laser 50 and the lens 52 forselectively exciting the sample. Fluorescent light generated by laserirradiation is taken out along the X-axis direction perpendicular to theY-axis direction, and converged through a condenser lens 62. Then, alight component having a specific wavelength to be detected is selectedfrom the fluorescent light by a filter 64 and is focused through animage-forming lens 66 at an optical sensor 68 such as a two-dimensionalCCD sensor. A signal detected by the optical sensor 68 is fed to asignal processor 70, being processed to identify the kind of theterminal base on the basis of the wavelength of the fluorescent light,and the base sequence of the nucleic acid sample is analyzed on thebasis of the measured signal.

[0033] In determination of the base sequence of a DNA (DeoxyribonucleicAcid), measurement is generally performed for four kinds of wavelengths.Fluorescent dyes are previously combined in the reaction operation sothat each maximum wavelength corresponds to the kind of a terminal baseof a DNA fragment.

[0034] A drain adaptor 46 is mounted on the upper end of the sheath flowcell 40. The sample, which has flowed from the capillary 20 into thesheath flow cell 40, is discharged as a wastage into a drain bottle 49through a drain tube 47. In the course of the drain tube 47 is provideda flow controller composed of an orifice and a plurality of capillariesfor controlling the flow rate of the sample by making constant thepassage resistance of the drain tube 47.

[0035] The entire operation of the electrophoresis analysis apparatus inthis embodiment will be described below.

[0036] Samples to be analyzed are previously poured in specific amountsinto 48 pieces of the sample vessels of each of the sample trays 100A,100B and 100C. The sample trays 100A, 100B and 100C in which the samplesare contained are fixed on the sample tray holder 14 with the set screwsS1 and S2. The controller 80 drives the vertically moving motor 16Z tomove down the moving mechanism 10 in the Z1 direction. The downwardmovement of the moving mechanism 10 is stopped at a position where thelower ends of the capillaries 20 are sufficiently separated from thebuffer bath 12. Then, the controller 80 drives the longitudinally movingmotor 16X to move the moving mechanism 10 in the X1 direction. Themovement of the moving mechanism 10 is stopped at a position where thesample tray 100A is located directly under the capillaries 20. Thecontroller 80 also drives the vertically moving motor 16Z to move up themoving mechanism 10 in the Z2 direction. The upward movement of themoving mechanism 10 is stopped at a position where the leading ends ofthe capillaries 20 are to be inserted in the samples in the samplevessels of the sample tray 100A. The positioning in the verticalmovement and the longitudinal movement of the moving mechanism 10 isperformed by a position detecting mechanism such as a switch provided inthe moving mechanism 10.

[0037] By applying a high voltage from the high voltage power supply 30between the sample tray 100A and the coupler 26 in a state in which thelower ends of the capillaries 20 are inserted in the samples, thesamples in the sample vessels are introduced into the capillaries 20.

[0038] The controller 80 drives the vertically moving motor 16Z to movedown the moving mechanism 10 in the Z1 direction. The downward movementof the moving mechanism 10 is stopped at a position where the lower endsof the capillaries 20 are sufficiently separated from the sample trays100A. Then, the controller 80 drives the longitudinally moving motor 16Xto move the moving mechanism 10 in the X2 direction. The movement of themoving mechanism 10 is stopped at a position where the buffer bath 12 islocated directly under the capillaries 20. The controller 80 also drivesthe vertically moving motor 16Z to move up the moving mechanism 10 inthe Z2 direction. The upward movement of the moving mechanism 10 isstopped at a position where the leading ends of the capillaries 20 areinserted in the buffer in the buffer bath 12. The positioning in thevertical movement and the longitudinal movement of the moving mechanism10 is performed using a position detecting mechanism such as a switchprovided in the moving mechanism 10.

[0039] By applying a high voltage from the high voltage power supply 30between the platinum electrode 13 and the coupler 26 in a state in whichthe lower ends of the capillaries 20 are inserted in the buffer, thesamples introduced in the capillaries 20 are separated byelectrophoresis.

[0040] After the analysis of the samples in the sample tray 100A iscompleted, the samples in the sample trays 100B and 100C are introducedin the capillaries 20 in the same procedure as described above, to bethus separated by electrophoresis.

[0041] It takes about two hours to analyze one sample, and therefore, byprovision of the three sample trays 100A, 100B and 100C on the sampletray holder 14 as shown in FIG. 1, it becomes possible to carry outautomatic analysis for about six hours. The number of the sample traysis not limited to three pieces but may be four pieces or more.

[0042] The method of optically detecting the sample separated byelectrophoresis is not limited to fluorescent light detection but may beabsorbance detection.

[0043] The configuration of a sample vessel used in the electrophoresisanalysis apparatus of the present invention will be described withreference to FIGS. 2 and 3.

[0044]FIG. 2 is a plan view of sample vessels used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention, and FIG. 3 is a sectional view taken on line A-A ofFIG. 2.

[0045] A sample tray 100 is formed into a rectangular shape in a planview, in which 48 pieces of circular sample vessels 100-1, 100-2, . . ., 100-48 are aligned. The sample tray 100 includes an upper sample plate102 and a metal base 104 fixed on the backface of the sample plate 102.The sample plate 102 is made from a transparent polyacrylate orpolymethacrylate resin, and has 48 pieces of circular openings forforming the sample vessels 100-1, 100-2, . . . , 100-48. The sampleplate 102 may be made from a transparent plastic material such aspolyvinyl chloride or polycarbonate. Since the sample plate 102 is madefrom a transparent material, it is possible to easily, visually confirmsamples contained in the sample vessels 100-1, 100-2, . . . , 100-48 andthe states of the capillaries inserted in the samples.

[0046] The sample plate 102 is fixed on the metal base 104 with eightscrews. The metal base 104 is made from a stainless steel as aconductive material. The metal base 104 forms part of wall surfaces ofthe sample vessels 100-1, 100-2, . . . , 100-48, and is used as anelectrode common to samples contained in the sample vessels 100-1, . . ., 100-2, 100-48. Since the metal base 104 forms part of the samplevessels, it is possible to eliminate the necessity of insertingelectrodes in the samples as in the conventional apparatus. It isexperimentally confirmed that the metal base 104 made from even astainless steel which is a widely available material exhibits asufficient durability. The electrophoresis analysis apparatus using themetal base 104 made from a stainless steel is allowed to be continuouslyused for a period of sixth months or more only by periodically washingthe sample tray 100. The conventional electrophoresis analysis apparatusis expensive because of use of a noble metal such platinum as anelectrode material; however, in the electrophoresis analysis apparatusof the present invention, the use of a stainless steel as an electrodematerial advantageously reduces the cost of the sample vessels.

[0047] Both end portions of the metal base 104 have circular holes 104A,and as described with reference to shown in FIG. 1, the sample tray 100is fixed on the metal made sample tray holder with the set screwspassing through the circular holes 104A.

[0048] The means for fixing the sample tray 100 on the sample trayholder is not limited to the set screws but may be plate springs or thelike.

[0049] In place of the metal base 104, there may be used an insulatingsubstrate on which a metal foil is stuck or a metal film is formed byvapor-deposition or sputtering. At this time, the metal foil or metalfilm forms part of the wall surfaces of the sample vessels, and itfunctions as a common electrode when it is made electrically conductiveto the samples contained in the sample vessels.

[0050] As will be described later, a packing is inserted between thesample plate 102 and the metal base 104 for preventing leakage ofsamples in the sample vessels.

[0051] A length L1 of the sample plate 102 is set at 160 mm. A distanceL2 from the center of the sample vessel 100-1 formed in the sample plate102 to the center of the sample vessel 100-48 formed in the sample plate102 is set at 141 mm. That is to say, a pitch P between the adjacentsample vessels is set at 3 mm. While the cross-sectional shape of thesample vessel will be described with reference to FIG. 3, an openingdiameter of the uppermost portion of the sample vessel is set at φ 2.8mm.

[0052] The pitch P between the adjacent sample vessels is set at a valueobtained by dividing a pitch (9 mm) between adjacent holes formed in amicrotiter plate by an integer number. The microtiter plate is generallyused for preparation of samples. The pitch between adjacent pipets usedfor pipetting samples from the microtiter plate is equal to the pitchbetween the adjacent holes of the microtiter plate. If the pitch Pbetween the adjacent sample vessels is, as described above, set at thevalue obtained by dividing the pitch (9 mm) between the adjacent holesof the microtiter plate by an integer number (for example 3 as shown inFIG. 2), that is, if the pitch P between the adjacent sample vessels isset at 3 mm, the samples can be pipetted from the microtiter plate intothe sample vessels using the existing pipets. To be more specific, atthe first pipetting, samples are poured in every fourth sample vessel,that is, in the order of the sample vessels 100-1, 100-4, . . . ,100-46. At the second pipetting, after the pipets are shifted only 3 mm,samples are poured in every fourth sample vessel, that is, in the orderof the sample vessels 100-2, 100-5, . . . , 100-47. At the thirdpipetting, after the pipets are shifted only 3 mm, samples are poured inevery fourth sample vessel, that is, in the order of the sample vessels100-3, 100-6, . . . , 100-48. In this way, while the pipetting of thesamples is divided into three times, the samples can be poured in thesample vessels using the existing pipets.

[0053] The pitch P between the adjacent sample vessels, which is set atthe value obtained by dividing the pitch (9 mm) between the adjacentholes of the microtiter plate, may be generally in a range of ½ to ¼ ofthe pitch (9 mm) between the adjacent holes of the microtiter plate inconsideration of the poured amount of the sample and the dimension ofthe sample vessel.

[0054] The cross-sectional structure of the sample tray 100 will bedescribed with reference to FIG. 3 which is an enlarged sectional viewtaken on line A-A of FIG. 2.

[0055] The sample plate 102 is fixed on the metal base 104 with the setscrews as described with reference to FIG. 2. A groove is formed in thelower surface portion of the sample plate 102, and a packing 106 ispreviously inserted in the groove for preventing leakage of liquid froma space between the sample plate 102 and the metal base 104. The packing106 is made from silicon rubber.

[0056] The cross-section of the sample plate 102 has a stepped portion102B, a taper portion 102C, and a cylindrical portion 102D. The steppedportion 102B is formed into an elliptic shape as shown in FIG. 2, and ithas a width W of 6 mm. When a height H of the sample plate 102 is 7 mm,a height H1 of the stepped portion 102B is 1.5 mm.

[0057] The taper portion 102C is formed into a cone shape having a taperangle θ of 24.4°. An opening diameter R1 of the taper portion 102C onthe upper end side is φ 2.8 mm, and an opening diameter R2 of the taperportion 102C on the lower end side is φ 1.2 mm. The taper portion 102Callows easy insertion of a pipet or capillary in the sample vessel, andspecifically, the taper portion 102C allows the leading end of the pipetor capillary to be easily bottomed. A height H2 of the taper portion102C is set at 3.7 mm.

[0058] The cylindrical portion 102D has an opening diameter R2 of φ 1.2mm and a height H3 of 1 mm. Assuming that the poured amount of a sampleis 5 μl, the sample is contained substantially in the cylindricalportion 102D.

[0059] On the other hand, each metal pin 108 is previously press-fittedin the metal base 104. The number of the metal pins 108 is the same asthat of the sample vessels, that is, 48 pieces in this embodiment. Themetal pin 108 is made from the same material as that of the metal base104, that is, a stainless steel. The leading end of the metal pin 108has a projecting portion 108A having a diameter R3 of φ 0.8 mm. In astate in which the sample plate 102 is fixed on the metal base 104, theprojecting portion 108A of the metal pin 108 slightly projects into thecylindrical portion 102D of the sample plate 102. With thisconfiguration, the sample is certainly brought in electric-contact withthe metal pin 108 and the metal base 104 used as an electrode.

[0060] In general, bubbles caused when a sample is poured in the samplevessel using a pipet possibly adhere on a wall surface of the samplevessel. If the bubbles adhere on the lowermost portion of the samplevessel and the capillary is inserted in the bubbles, the sample cannotbe introduced into the capillary. To cope with such an inconvenience,the projecting portion 108A is provided in such a manner as to projectinto the cylindrical portion 102D. In this case, even if bubbles adhereon the bottom of the sample vessel, since the capillary is only insertedto the leading end of the projecting portion 108A, the sample can beintroduced into the capillary by reducing the effect of the bubbles.

[0061] The opening diameter R1 of the upper end of the taper portion102C which forms part of the sample vessel is set at φ 7 mm or lessdepending on the poured amount of a sample. In particular, if the pouredamount of a sample is small, the opening diameter R1 is set at φ 3 mm orless, for example, φ 2.8 mm as described above. If the poured amount ofa sample is smaller than that described above, the opening diameter R1may be set at φ 2 mm or less.

[0062] As described above, while the sample tray 100 has a large number(48 pieces) of the sample vessels, since the conductive metal base andmetal pins form part of the sample vessels and are taken as a commonelectrode, the necessity of inserting electrodes in the sample vesselsas in the conventional apparatus can be eliminated. As a result, sinceonly the capillaries may be inserted in the sample vessels, thepreparation for analysis can be facilitated.

[0063] As described with reference to FIG. 1, since 48 pieces of thecapillaries arranged in parallel are fixed in position by the capillaryretaining plate 22, the capillaries of the multi-capillary type can beeasily inserted in the sample vessels only by moving the sample tray 100upward using the moving mechanism 10. As a result, the electrophoresisanalysis can be automated using the electrophoresis analysis apparatushaving the configuration shown in FIG. 1.

[0064] The configuration of a second sample vessel used for theelectrophoresis analysis apparatus of the present invention will bedescribed with reference to FIG. 4.

[0065]FIG. 4 is a plan view of the second sample vessels used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention.

[0066] A sample tray 100′ in this embodiment is different from thesample tray 100 shown in FIG. 2 in that sample vessels 100-1, 100-2, . .. , 100-48 are arranged in a staggered pattern. The cross-sectionalshape of the sample vessel is the same as described with reference toFIG. 3.

[0067] The sample tray 100′ has a rectangular shape in a plan view, inwhich 48 pieces of the circular sample vessels 100-1, 100-2, . . . ,100-48 are arranged in a staggered pattern. The sample tray 100′ has anupper sample plate 102′ and a metal base 104 fixed on the backface ofthe sample plate 102′. The sample plate 102′ is made from a transparentacrylic resin, and has 48 pieces of circular openings for forming thesample vessels 100-1, 100-2, . . . , 100-48.

[0068] The sample plate 102′ is fixed on the metal base 104 with eightscrews. The metal base 104 is made from a stainless steel as aconductive material. The metal base 104 forms part of wall surfaces ofthe sample vessels 100-1, 100-2, . . . , 100-48, and is used as anelectrode common to samples contained in the sample vessels 100-1, . . ., 100-2, 100-48. Since the metal base forms part of the sample vessels,it is possible to eliminate the necessity of inserting electrodes insamples as in the conventional apparatus.

[0069] Both end portions of the metal base 104 have circular holes 104A.As described with reference to FIG. 1, the sample tray 100′ is fixed ona metal made sample tray holder with set screws.

[0070] As described with reference to FIG. 3, a packing is insertedbetween the sample plate 102′ and the metal base 104 for preventingleakage of samples in the sample vessels.

[0071] A length L3 of the sample plate 102′ is set at 128 mm. A distanceL4 from the center of the sample vessel 100-1 formed in the sample plate102′ to the center of the sample vessel 100-48 formed in the sampleplate 102′ is set at 106 mm. A pitch P between the adjacent samplevessels is set at 3 mm.

[0072] By arranging the sample vessels in the sample tray 100′ in thestaggered pattern, the length of the sample tray 100′ can be shortened,to thereby miniaturize the electrophoresis analysis apparatus,particularly, the moving mechanism.

[0073] The configuration of a third sample vessel used for theelectrophoresis analysis apparatus of the present invention will bedescribed with reference to FIG. 5.

[0074]FIG. 5 is a plan view of the third sample vessels used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention.

[0075] A sample tray 100″ in this embodiment is different from thesample tray 100 or 100′ shown in FIG. 2 or 4 in that 4 n pieces ofsample vessels 100-11, 100-12, . . . , 100-21, . . . , 100-31, . . . ,100-41, . . . , 100-4 n are arranged in four rows. The cross-sectionalshape of the sample vessel is the same as described with reference toFIG. 3.

[0076] The sample tray 100″ has a rectangular shape in a plan view, inwhich 4 n pieces of the circular sample vessels 100-11, 100-12, . . . ,100-21, . . . , 100-31, . . . , 100-41, . . . , 100-4 n are arranged ina matrix pattern of four rows (n pieces for each row). The sample tray100″ has an upper sample plate 102″ and a metal base 104 fixed on thebackface of the sample plate 102″. The sample plate 102″ is made from atransparent acrylic resin, and has 4 n pieces of circular openings forforming the sample vessels 100-11, . . . , 100-4 n.

[0077] The sample plate 102″ is fixed on the metal base 104 with screws.The metal base 104 is made from a stainless steel as a conductivematerial. The metal base 104 forms part of wall surfaces of the samplevessels 100-11, 100-4 n, and is used as an electrode common to samplescontained in the sample vessels 100-11, . . . , 100-4 n. Since the metalbase forms part of the sample vessels, it is possible to eliminate thenecessity of inserting electrodes in samples as in the conventionalapparatus.

[0078] The sample tray 100″ is fixed on a metal made sample tray holderwith set screws. As described with reference to FIG. 3, a packing isinserted between the sample plate 102″ and the metal base 104 forpreventing leakage of samples in the sample vessels. A pitch P betweenthe adjacent sample vessels is set at a value obtained by dividing apitch (9 mm) between adjacent holes of the microtiter plate by aninteger number.

[0079] By arranging a plurality of rows of the sample vessels in thesample tray 100″, the length of the sample tray 100″ can be shortened,to thereby miniaturize the electrophoresis analysis apparatus,particularly, the moving mechanism.

[0080] The cross-sectional structure of a fourth sample vessel used forthe electrophoresis analysis apparatus of the present invention will bedescribed with reference to FIG. 6.

[0081]FIG. 6 is a sectional view of the fourth sample vessel used forthe electrophoresis analysis apparatus according to one embodiment ofthe present invention. In addition, the planar shape of a sample tray inwhich a plurality of the sample vessels are arranged is the same as thatshown in FIG. 2, 4 or 5.

[0082] A sample tray 100A in this embodiment includes a sample plate102E composed of a transparent plate made from an acrylic resin, aninsulating base 104B, a packing 106 made from silicon rubber, and metalpins 108 made from a conductive material such as a stainless steel. Thesample plate 102E has a taper portion functioning as a sample vessel.That is to say, a sample is contained in the taper portion of the sampleplate 102E. The metal pin 108 is brought in electric-contact with asample and functions as an electrode. Since a plurality of the samplevessels are formed in the sample tray 100A, the metal pins 108 of thesame number as that of the sample vessels are provided in such a manneras to be electrically connected to the metal made sample tray holdershown in FIG. 1.

[0083] The sample plate 102E is fixed on a base 104B with screws. Agroove is formed in a lower surface portion of the sample plate 102E,and a packing 106 is previously inserted in the groove for preventingleakage of liquid from a space between the sample plate 102E and thebase 104B.

[0084] By independently connecting a plurality of the metal pins 108 toa high voltage power supply and also connecting a current detectioncircuit between each metal pin and the high voltage power supply, it ispossible to monitor a current for each sample.

[0085] The cross-sectional structure of a fifth sample vessel used forthe electrophoresis analysis apparatus of the present invention will bedescribed with reference to FIG. 7.

[0086]FIG. 7 is a sectional view of the fifth sample vessel used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention. In addition, the planar shape of a sample tray inwhich a plurality of the sample vessels are arranged is the same as thatshown in FIG. 2, 4 or 5.

[0087] A sample tray 100B in this embodiment includes a metal madesample plate 102F, an insulating base 104C, and a packing 106 made fromsilicon rubber. The sample plate 102F is formed with a taper portionfunctioning as a sample vessel. That is to say, a sample is contained inthe taper portion of the sample plate 102F. Further, the sample plate102F made from a conductive material has a function as an electrode.

[0088] The sample plate 102F is fixed on the base 104C with screws. Agroove is formed in an upper surface portion of the base 104C, and apacking 106 is previously inserted in the groove for preventing leakageof liquid from a space between the sample plate 102F and the base 104C.

[0089] The cross-sectional structure of a sixth sample vessel used forthe electrophoresis analysis apparatus of the present invention will bedescribed with reference to FIG. 8.

[0090]FIG. 8 is a sectional view of the sixth sample vessel used for theelectrophoresis analysis apparatus according to one embodiment of thepresent invention. In addition, the planar shape of a sample tray inwhich a plurality of the sample vessels are arranged is the same as thatshown in FIG. 2, 4 or 5.

[0091] A sample tray 100C in this embodiment includes an insulatingsample plate 102G, an insulating base 104D, a packing 106A made fromsilicon rubber, and a metal seat 109. The sample plate 102G has a taperportion functioning as a sample vessel. That is to say, a sample iscontained in the taper portion of the sample plate 102G.

[0092] The sample plate 102G is fixed on the base 104D with screws. Themetal seat 109 and the packing 106A made from silicon rubber are heldbetween the sample plate 102G and the base 104D. The metal seat 109 isbrought in contact with a sample and functions as an electrode. Thepacking 106A prevents leakage of liquid from a space between the sampleplate 102G and the base 104D.

[0093] The cross-sectional structure of a seventh sample vessel used forthe electrophoresis analysis apparatus of the present invention will bedescribed with reference to FIG. 9.

[0094]FIG. 9 is a sectional view of the seventh sample vessel used forthe electrophoresis analysis apparatus according to one embodiment ofthe present invention. In addition, the planar shape of a sample tray inwhich a plurality of the sample vessels are arranged is the same as thatshown in FIG. 2, 4 or 5.

[0095] A sample tray 100D in this embodiment includes an insulatingsample plate 102H, an insulating base 104C, a packing 106B made fromsilicon rubber, and a metal wire 109A. The sample plate 102H has a taperportion functioning as a sample vessel. That is to say, a sample iscontained in the taper portion of the sample plate 102H.

[0096] The sample plate 102H is fixed on the base 104C with screws. Themetal wire 109A and the packing 106B made from silicon rubber are heldbetween the sample plate 102H and the base 104C. The metal wire 109A isbrought in contact with a sample and functions as an electrode. Thepacking 106B prevents leakage of liquid from a space between the sampleplate 102H and the base 104C.

[0097] The structure of an electrode portion of an eighth sample vesselused for the electrophoresis analysis apparatus of the present inventionwill be described with reference to FIG. 10.

[0098]FIG. 10 is a plan view of an electrode portion of the eighthsample vessel used for the electrophoresis analysis apparatus accordingto one embodiment of the present invention. In addition, the planarshape of a sample tray in which a plurality of the sample vessels arearranged is the same as that shown in FIG. 2, 4 or 5. Thecross-sectional structure is also the same as that shown in, forexample, in FIG. 8.

[0099] In this embodiment, a metal film is formed on an insulating base104C by vapor-deposition, and electrode patterns 109B are formed byselective etching. The electrode patterns 109B are connected to a highvoltage power supply via a connector 110.

[0100] The structure of a ninth sample vessel used for theelectrophoresis analysis apparatus of the present invention will bedescribed with reference to FIG. 11.

[0101]FIG. 11 is a plan view of an electrode portion of the ninth samplevessel used for the electrophoresis analysis apparatus according to oneembodiment of the present invention.

[0102] In this embodiment, metal made projections 104F1 and 104F2 areintegrally formed on a base 104F made from a metal such as a stainlesssteel. Insulating rings 103A and 103B are inserted around theprojections 104F1 and 104F2 respectively, to form sample vessels.

[0103] The base 104F functions as an electrode for each sample vessel.

[0104] As the conductive material forming part of the sample vessel, aconductive rubber or conductive organic material may be used in place ofa metal.

[0105] In the above description, part of the sample tray is made from aconductive material; however, the entire sample tray may be made from ametal.

[0106] As described above, according to this embodiment, since part of aplurality of the sample vessels provided on a sample tray are made froma conductive material and are taken as a common electrode, the necessityof inserting electrodes in the sample vessels as in the conventionalapparatus can be eliminated. As a result, since only the capillaries maybe inserted in the sample vessels, the preparation for analysis can befacilitated.

[0107] By arranging a plurality of the capillaries in parallel andfixing them in position by a capillary retaining plate, the capillariesof the multi-capillary type can be easily inserted in the sample vesselsonly by moving the sample tray upward using a moving mechanism. As aresult, the electrophoresis analysis can be automated using theelectrophoresis analysis apparatus of the present invention.

[0108] While the preferred embodiments have been described usingspecific terms, such description is for illustrative purposes only, andit is understood that many changes and variations may be made withoutdeparting from the spirit or scope of the following claims.

What is claimed is:
 1. An electrophoresis analysis apparatus comprising:a plurality of migration passages; a sample tray holder capable ofremovably fixing a sample tray including a plurality of sample vesselsfor containing samples; a detector for optically detecting samplecomponents separated by electrophoresis; a power supply for applying avoltage to the migration passages, wherein said sample tray comprises anelectrode capable of contacting the sample in at least one of saidplurality of sample vessels; wherein a part of the sample tray holder iselectrically connected to the power supply; and wherein said part of thesample tray holder is electrically connected to said electrode inresponse to fixing the sample tray on the sample tray holder.
 2. Anelectrophoresis analysis apparatus according to claim 1, wherein thepart of the sample vessel is transparent.
 3. An electrophoresis analysisapparatus according to claim 1, wherein the electrode is made of astainless steel.
 4. An electrophoresis analysis apparatus according toclaim 1, and further comprising a current detection circuit to monitor acurrent for each sample.
 5. An electrophoresis analysis apparatusaccording to claim 1, wherein the sample tray comprises a plate portionhaving a plurality of openings and a metal base portion fixed on abottom portion of the plate portion.
 6. An electrophoresis analysisapparatus according to claim 5, wherein the sample tray furthercomprises metal pins fixed on the metal base portion, the metal pinshaving portions projecting in the openings of the plate portion.
 7. Anelectrophoresis analysis apparatus according to claim 1, wherein thesample tray comprises a metal plate portion having a plurality ofopenings and a base portion fixed on a bottom portion of the plateportion.
 8. An electrophoresis analysis apparatus according to claim 1,wherein the sample tray comprises a plate portion having a plurality ofopenings; a base portion fixed on a bottom portion of the plate portion;and a plate or wire made of conductive material, the plate or wire beingin contact with samples.
 9. An electrophoresis analysis apparatuscomprising: a migration passage; a sample tray holder capable ofremovably fixing a sample tray including a sample vessel for containinga sample; a detector for optically detecting sample components separatedby electrophoresis; a power supply for applying a voltage to themigration passage, wherein said sample tray comprises an electrodecapable of contacting the sample in said sample vessel; wherein a partof the sample tray holder is electrically connected to the power supply;and wherein said part of the sample tray holder is electricallyconnected to said electrode in response to fixing the sample tray on thesample tray holder.
 10. An electrophoresis analysis apparatus accordingto claim 9, wherein the part of the sample vessel is transparent.
 11. Anelectrophoresis analysis apparatus according to claim 9, wherein theelectrode is made of a stainless steel.
 12. An electrophoresis analysisapparatus according to claim 9, and further comprising a currentdetection circuit to monitor a current for a sample.
 13. Anelectrophoresis analysis apparatus according to claim 9, wherein thesample tray comprises a plate portion comprising an opening and a metalbase portion fixed on a bottom portion of the plate portion.
 14. Anelectrophoresis analysis apparatus according to claim 13, wherein thesample tray further comprises a metal pin fixed on the metal baseportion, the metal pin comprising a portion projecting in the opening ofthe plate portion.
 15. An electrophoresis analysis apparatus accordingto claim 9, wherein the sample tray comprises a metal plate portioncomprising an opening and a base portion fixed on a bottom portion ofthe plate portion.
 16. An electrophoresis analysis apparatus accordingto claim 9, wherein the sample tray comprises a plate portion comprisingan opening; a base portion fixed on a bottom portion of the plateportion; and a plate or wire made of conductive material, the plate orwire being in contact with sample.